title: Involvement of STIM1 and Orai1 in EGF-mediated cell growth in retinal pigment epithelial cells.
abstract: BACKGROUND
  In non-excitable cells, one major route for calcium entry is through store-operated calcium (SOC) channels in the plasma membrane. These channels are activated by the emptying of intracellular Ca²⁺ store. STIM1 and Orai1 are major regulators of SOC channels. In this study, we explored the functions of STIM1 and Orai1 in epidermal growth factor (EGF)-induced cell proliferation and migration in retinal pigment epithelial cells (ARPE-19 cell line).
  
  
  RESULTS
  EGF triggers cell proliferation and migration in ARPE-19 cells. Cell proliferation and migration involve STIM1 and Orai1, as well as phosphorylation of extracellular signal-regulated protein kinase (ERK) 1/2, and Akt. Pharmacological inhibitors of SOC channels and siRNA of Orai1 and STIM1 suppress cell proliferation and migration. Pre-treatment of mitogen-activated protein kinase kinase (MEK) inhibitors and a phosphatidylinositol 3 kinases (PI3K) inhibitor attenuated cell proliferation and migration. However, inhibition of the SOC channels failed to prevent EGF-mediated ERK 1/2 and Akt phosphorylation.
  
  
  CONCLUSIONS
  Our results showed that STIM1, Orai1, ERK 1/2, and Akt are key determinants of EGF-mediated cell growth in ARPE-19 cells. EGF is a potent growth molecule that has been linked to the development of PVR, and therefore, STIM1, Orai1, as well as the MEK/ERK 1/2 and PI3K/Akt pathways, might be potential therapeutic targets for drugs aimed at treating such disorders.
authors.affiliation: Department of Medical Genetics, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: I-Hui
authors.initials: IH
authors.lastname: Yang
authors.forename: Yao-Ting
authors.initials: YT
authors.lastname: Tsai
authors.forename: Siou-Jin
authors.initials: SJ
authors.lastname: Chiu
authors.forename: Li-Teh
authors.initials: LT
authors.lastname: Liu
authors.forename: Hsuan-Hung
authors.initials: HH
authors.lastname: Lee
authors.forename: Ming-Feng
authors.initials: MF
authors.lastname: Hou
authors.forename: Wen-Li
authors.initials: WL
authors.lastname: Hsu
authors.forename: Ben-Kuen
authors.initials: BK
authors.lastname: Chen
authors.forename: Wei-Chiao
authors.initials: WC
authors.lastname: Chang
mesh_terms: D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D004815:Epidermal Growth Factor / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D000071740:ORAI1 Protein; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000378:metabolism*; D015398:Signal Transduction; D000071737:Stromal Interaction Molecule 1
chemical_list: D015220:Calcium Channels; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D004815:Epidermal Growth Factor; D051057:Proto-Oncogene Proteins c-akt; D020929:Mitogen-Activated Protein Kinase Kinases; D002118:Calcium